Clinical management of plant food allergy in patients sensitized to lipid transfer proteins is heterogeneous: identifying the gaps.

BACKGROUND AND OBJECTIVE: Patients sensitized to lipid transfer protein (LTP) present a wide clinical variability. The lack of practical diagnostic and therapeutic guidelines complicate their management. The aim of the study was to describe the clinical approach of Spanish allergists to this pathology using a survey designed by PICO method and subsequent Delphi approach validation. METHODS: Designed survey was answered by 224 allergists (75% women; 57.1% with >20 years of professional experience). Homogeneity regarding clinical practice on the main points of LTP allergy diagnosis was observed, except for patients with suspected NSAID hypersensitivity (44.6% frequently include LTP skin testing). Oral food challenges were not frequently performed (63.6% occasionally to never), and they were generally (75.5%) used to confirm tolerance. It was common to recommend fruit skins avoidance (77.2%) and maintaining consumption of foods to which patients are sensitised but tolerant (99.1%). RESULTS: There was heterogeneity on other dietary indications, modifications due to co-factors, or traces avoidance. Peach sublingual immunotherapy (SLIT) was considered very/quite effective by 55.9% of allergists. The majority (79.5%) consider SLIT indicated in <25% of LTP allergic patients, based on severity (95.2%), frequency of reactions (99.4%), allergy to multiple food families (97.4%), and the quality of life/nutrition impairment (91.5%). There was different practice on SLIT prescription based on co-factor involvement. CONCLUSION: These data suggest that there is a need to increase evidence to reduce the clinical practice heterogeneity in the management of LTP allergy.

Diagnostic precision of local and World Health Organization definitions of symptomatic COVID-19 cases: an analysis of Mexico's capital.

OBJECTIVES: Case definitions are vital in a pandemic to effectively identify, isolate, and contact trace, particularly where testing is slow, scant, or not available. While case definitions have been developed in the COVID-19 pandemic, their diagnostic properties have not been adequately assessed. This study's objective is to determine the diagnostic properties of local and World Health Organization (WHO) COVID-19 case definitions in the large metropolitan area of Mexico City. METHODS: We calculated the diagnostic properties of five COVID-19 definitions (three of the Mexican government and two of the WHO) using open data of suspected COVID-19 cases in Mexico City from March 24th, 2020, until May 15th, 2021. RESULTS: All 2,564,782 people included in the analysis met the WHO suspected case definition (sensitivity: 100%, specificity: 0%). The WHO probable case definition was met by 1.2%, while the first and second Mexican suspected case had sensitivities of 61% and specificities of 61% and 67%, respectively. Confirmed case by epidemiological contact had a low sensitivity (32%) but slightly higher specificity (81%). CONCLUSIONS: Case definitions should maximize sensitivity, especially in a high-transmission area such as Mexico City. The WHO suspected case definition has the potential for detecting most symptomatic cases. We underline the need for routine evaluation of case definitions as new evidence arises to maximize their usefulness.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Quinolones.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review.

BACKGROUND: Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE. METHODS: We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible. RESULTS: We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference -0.74 on a 20-point scale (95% CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -3.69, -4.71). Meta-analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT, for example investigator-rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low. CONCLUSION: We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.

The cost-effectiveness of bevacizumab for the treatment of advanced ovarian cancer in Canada.

BACKGROUND: The overall survival (os) analysis of the icon7 trial demonstrated that frontline ovarian cancer patients with a high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease) benefited from the addition of bevacizumab to standard chemotherapy compared with standard chemotherapy alone. The objective of the present study was to investigate the cost-effectiveness, from a Canadian publicly funded perspective, of adding bevacizumab to frontline treatment of ovarian cancer at high risk of progression. METHODS: An area-under-the-curve, Markov-structured model was used to estimate the cost-effectiveness of the treatments. Long-term progression-free survival (pfs) and os were extracted from the icon7 trial (subgroup at high risk of relapse) and extrapolated by parametric time-to-event functions over a time horizon of 10 years. Canadian pfs health state utility values were obtained from the EQ-5D (EuroQoL Group, Rotterdam, Netherlands) questionnaires in the icon7 high-risk patient population. Canadian post-progression utility values were consistent with those for other gynecologic cancers. Cost inputs were informed by public sources. An annual 5% efficacy and cost discount rate was applied. A probabilistic sensitivity analysis and one-way sensitivity analyses were conducted. RESULTS: Ovarian cancer patients at high risk of progression receiving bevacizumab plus standard chemotherapy experienced a mean incremental quality-adjusted life year (qaly) gain of 0.374 years. At an additional cost of $35,901.54, the incremental cost-effectiveness ratio (icer) for the addition of bevacizumab to standard chemotherapy, relative to standard chemotherapy alone, was $95,942 per qaly. CONCLUSIONS: No formal health technology assessment willingness-to-pay threshold exists in Canada. However, at a threshold of $100,000 per qaly, bevacizumab in addition to chemotherapy is a cost-effective alternative for ovarian cancer patients who are at high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease). Using the $100,000 per qaly threshold in a probabilistic sensitivity analysis, it was determined that, compared with standard chemotherapy, the addition of bevacizumab to chemotherapy is cost-effective in 56% of tested scenarios.

Neutralization of mitochondrial superoxide by superoxide dismutase 2 promotes bacterial clearance and regulates phagocyte numbers in zebrafish.

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death. Pseudomonas aeruginosa is an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated with P. aeruginosa are capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response to P. aeruginosa infection. sod2 is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharide in vitro, and sod2 knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.

A review of the management of elderly patients with non-small-cell lung cancer.

Most patients with non-small-cell lung cancer (NSCLC) are elderly but evidence to guide appropriate treatment decisions for this age group is generally scant. Careful evaluation of the elderly should be undertaken to ensure that treatment appropriate for the stage of the tumour is guided by patient characteristics and not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred option, but briefer tools may be appropriate to select patients for further evaluation. The predicted outcome should be used to guide management decisions together with a reappraisal of polypharmacy. Patient expectations should also be taken into account. Management recommendations are generally similar to those of general guidelines for the NSCLC population, although the risks of surgery and toxicity of chemotherapy and radiotherapy are often increased in the elderly compared with younger patients; therefore, patients should be closely scrutinised and subjected to a CGA to ensure suitability of the planned treatment. If surgery is indicated, then lobectomy is generally the preferred option, although limited resection may be more feasible for some. Radiotherapy with curative intent is an alternative, with stereotactic body radiotherapy the most likely preferred modality. Adjuvant chemotherapy is also an appropriate approach, whereas adjuvant radiotherapy is generally not recommended. Concurrent chemoradiotherapy should be considered for elderly patients with inoperable locally advanced disease and chemotherapy for advanced/metastatic disease. Efforts should also be made to increase participation of elderly patients with NSCLC in clinical trials, thereby enhancing evidence-based treatment decisions for this majority group. This will require overcoming barriers relating to trial design and to physician and patient awareness and attitudes.

Performance of different in vitro techniques in the molecular diagnosis of peanut allergy.

INTRODUCTION: Peanut allergy is an increasingly serious disorder with a heterogeneous pattern of sensitization across different countries. In vitro diagnostic techniques may help in establishing these patterns. OBJECTIVES: To analyze the usefulness of determining specific immunoglobulin E (sIgE) with the ImmunoCAP fluorescence enzyme immunoassay (FEIA), the ImmunoCAP ISAC CRD103 microarray (ISAC), and the basophil activation test (BAT) in the molecular diagnosis of peanut allergy. METHODS: In 26 peanut-allergic patients, sIgE antibodies against allergic components were measured with FEIA, ISAC, and BAT. RESULTS: The major peanut component in our population wasAra h 9.The detection of sIgE toAra h 9 using FEIA and BAT with this allergen yielded a sensitivity of 92% and 88% and a specificity of 95% and 100%, respectively. Overall diagnosis of peanut allergy by ISAC showed a sensitivity of 11% but a specificity of 95% since Ara h 9 was not present in the microarray version used. There was diagnostic agreement between the 3 techniques for the peanut allergens studied. CONCLUSIONS: The determination of sIgE to Ara h 9 using FEIA and BAT offers high sensitivity and specificity in the diagnosis of peanut allergy in the Spanish population. The CRD103 version of ISAC is not of value in our region as it does not include the most common allergen, Ara h 9.

Diagnosis of patients with immediate hypersensitivity to beta-lactams using retest.

BACKGROUND: beta-Lactams are the drugs most frequently involved in hypersensitivity reactions mediated by immunoglobulin (Ig) E. OBJECTIVE: To evaluate a population of patients with suspected B-lactam allergy using a validated algorithm that includes specific IgE antibodies, skin testing, and/or a drug provocation test. METHODS: A total of 1032 patients with symptoms compatible with B-lactam allergy were evaluated by means of their clinical history, specific immunoglobulin (Ig) E antibody determinations (benzylpenicillin, ampicillin, and amoxicillin), and skin tests with major determinants (penicilloyl-polylysine) and minor determinants (minor determinant mixture) of benzylpenicillin, penicillin G, ampicillin, and amoxicillin-clavulanic acid. Patients whose skin test results were negative were challenged with amoxicillin-clavulanic acid. Only immediate hypersensitivity reactions were evaluated. All patients with negative study results and for whom a reaction occurred more than 1 year before were retested using the same protocol. RESULTS: A total of 170 patients (16.4%) were finally confirmed as having immediate allergic reactions to beta-lactams (62.3% by skin testing, 16.5% by specific IgE, and 21.2% by drug provocation test). The mean age of these patients was 43.3 years, and the drug most frequently involved in the reaction was amoxicillin (41.1%), followed by the combination amoxicillin-clavulanic acid (36.4%). In the remaining 22.5%, different beta-lactams were involved or the culprit drug was not known. Only mild reactions were observed after the drug provocation test. A retest was required in 23% of patients in order to confirm their hypersensitivity. CONCLUSIONS: These results indicate that a diagnostic protocol based on the combination of skin testing and in vitro determination of specific IgE antibodies plus, if required, drug provocation testing is an appropriate procedure for evaluating immediate hypersensitivity reactions to beta-lactams. Because the sensitivity of skin testing and in vitro IgE assays is not optimal and a considerable proportion of patients are tolerant, drug provocation tests are necessary to achieve the diagnosis or confirm tolerance. A large percentage of patients (23%) were diagnosed using retest.

Drug hypersensitivity reactions: response patterns, drug involved, and temporal variations in a large series of patients.

BACKGROUND: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments, and are becoming more common due to increasing prevalence and case complexity. OBJECTIVE: To study the clinical characteristics, drugs involved, diagnostic methods, and temporal variation of DHRs in a large series of patients over a 6-year period. METHODS: We included all patients attending our department between 2005 and 2010. The diagnosis was performed by in vivo and/or in vitro tests (basophil activation test and specific immunoglobulin [Ig] E in serum and drug provocation testing [DPT]) when indicated. RESULTS: We evaluated 4460 patients who reported 4994 episodes (mean [SD] of 1.13 [0.36] [range, 1-3] episodes per patient). Based on clinical history, 37% of the episodes were attributed to nonsteroidal anti-inflammatory drugs (NSAIDs), 29.4% to beta-lactam antibiotics (BLs), 15% to non-BLs, and 18.4% to other drugs.Analysis of the 1683 patients (37.45%) finally confirmed as allergic showed the most frequent diagnosis to be hypersensitivity to multiple NSAIDs (47.29%), followed by immediate reactions to BLs (18.12%). There was an increase in reactions to non-BLs (from 21.2% to 31.9%; P < .03) over the study period, mainly due to an increase in allergy to quinolones (from 0.5% to 6.8%; P < .02); 44% of patients were diagnosed by clinical history, 14.6% by skin tests, 10.4% by in vitro tests, and 30.8% by DPT. CONCLUSIONS: NSAIDs were the drugs most frequently involved in DHRs and the most common diagnosis was urticaria/angioedema with cross intolerance. Reactions to emerging drugs such as quinolone derivatives and radiocontrast media are becoming more common.